| 151 | Melinda K. Duncan, Ph.D., FARVO | <p>Professor, Biological Sciences<br></p>
<p>Editorial board member, Investigative Ophthalmology and Visual Sciences</p>
<p>Trustee, Association for Research in Vision and Ophthalmology (ARVO)</p>
<p>Director, Education and Professional Development Core, Delaware IDeA Network for Biomedical Research Excellence (INBRE)</p>
<p>Associate Director, Center for Biomedical Research Excellence (COBRE) in Discovery of Chemical Probes and Therapeutic Leads </p> | (302) 831-0533 | (302) 831-2281 | duncanm@udel.edu | 327 Wolf Hall | 266 Wolf Hall | Department of Biological Sciences Wolf Hall University of Delaware Newark, DE 19716 | <ul>
<li><strong>B.S.</strong> - Lafayette College
</li><li><strong>Ph.D.</strong> - The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School and Rutgers the State University of New Jersey
</li><li><strong>Postdoctoral</strong> - The National Eye Institute, The National Institutes of Health </li></ul> | <ul>
<li><b>BISC 850- Introduction to grant writing, Fall 2018</b>
</li><li><b>BISC 833- Responsible conduct of research, Spring 2019</b> </li></ul> | <p>
<img src="/content-sub-site/PublishingImages/people/duncanm/mduncan-lens.jpg" alt="Lens isolated from an adult cow" class="ms-rtePosition-2" />The vertebrate lens is a remarkable tissue that has many evolutionary adaptations that allow it to remain transparent throughout life. Further, its cell biology is quite distinct from that of other tissues which results in it being the only epithelial organ which never develops clinically relevant cancers. Aging, ocular injury, genetic alterations or systemic diseases such as diabetes can lead to the loss of lens transparency, or cataract. Cataracts are the predominant cause of blindness worldwide and their incidence is increasing as life expectancies increase. Over the past thirty years, robust techniques to surgically treat cataract have been developed, greatly reducing cataract-related blindness in western countries. In the United States, cataract removal is the most common surgical procedure performed for any reason. While the short term visual outcome for patients undergoing cataract surgery is often excellent, a large proportion of operated eyes subsequently develop posterior capsular opacification (PCO), a condition often referred to as secondary cataract which requires additional treatment and can lead to poor vision in the long term. You can read a recent press release about ongoing work in the laboratory written for a lay audience <a href="https://www.udel.edu/udaily/2018/november/melinda-duncan-cataract-research-lens-cells/">here</a> and a recent interview on this topic can be found
<a href="/content-sub-site/Documents/People/duncanm/Eye%20on%20research%20interview%2012_18%201209DUNC.mp3">here</a>.<br></p><p>My laboratory focuses on understanding the pathogenesis of cataracts, the molecular mechanisms responsible for the side effects of cataract and other ocular surgeries, as well as the regulation of lens development and cellular differentiation.</p><p>Pursuit of such research projects opens you up to pursue a variety of
<a href="https://www.arvo.org/globalassets/arvo/advocacy/toolkits/seeyourfuturefinal.pdf">careers</a> in both academia and industry. Alumni from the laboratory work in a variety of professions ranging from academic research, college level teaching, industry-based research, science writing, core facilty operations, science advocacy, and consulting, </p> | <ul>
<li><strong>The mechanisms controlling posterior capsular opacification</strong> - Cataract surgery is a true marvel of modern medicine which has greatly reduced the burden of blindness, particularly in developed countries. However, like all surgeries, cataract surgery is not without its side effects. Posterior capsular opacification (PCO) results when lens cells remaining behind after surgery proliferate, migrate into the visual axis, and produce scar tissue which distorts the patient's vision. While this, the most common negative outcome of cataract surgery, can be treated as well, each further intervention reduces final visual outcome, and can cause or exacerbate other blinding ocular conditions such as retinal detachments and glaucoma. We have discovered that some integrins and extracellular matrix molecules are critical for PCO development. We are investigating the molecular mechanisms by which these molecules drive PCO in the hopes of identifying clinical interventions to block this potentially blinding condition. This work is supported by an R01 grant from the National Eye Institute
</li><li><strong>Mechanisms driving ocular inflammation following cataract surgery</strong>. We recently made the novel discovery that the lens cells remaining behind after cataract surgery rapidly (within 3 hours) induce the expression of numerous proinflammatory cytokines and other inflammatory mediators following cataract surgery. As post-surgical inflammation is a major problem following cataract surgery, this implies that the injured lens is the main signalling center regulating this undesirable side-effect. We are investigating both the molecular mechanisms that induce this massive inflamatory response and the potential role for cross-talk between ocular inflammation and posterior capsular opacificiation. This work is supported by an R01 grant from the National Eye Institute. Â
</li><li><strong>The regulation of lens fiber cell differentiation</strong> - The differentiation of lens fiber cells is marked by a major reorganization of cell structure and drastic changes in gene expression. While we have developed a good understanding of the growth and transcription factors that drive these changes in gene expression, we know very little about how this regulates the morphological changes necessary to form a transparent lens. We have performed RNAseq (next generation sequencing) to analyze the transcriptome of a mouse mutant which fails to undergo these morphological changes to discover genes likely to regulate this process. We are using a combination of mouse and chicken models to study the mechanisms controling lens morphogenesis using this set of candidate genes as a starting point.
</li><li><strong>Aniridia fibrosis syndrome</strong>- Aniridia is a genetic condition characterized by numerous ocular abnormalities including the lack of an iris and abnormalities of the retina that are apparent at birth. Later, Aniridia patients develop numerous other ocular complications including glaucoma, corneal scarring and cataracts and these patients usually require multiple surgeries to manage these conditions. However, aniridia patients often have poorer visual outcomes from these interventions than expected due to their tendency to develop massive ocular fibrosis (scarring) in response to these surgeries. We have evidence that the disruption of the Pax6 gene that causes Aniridia negatively impacts the normal wound healing response to ocular surgery and we are investigating the molecular mechanisms of this observation . The overall goal of this research is to identify interventions that can be used in the clinic to prevent aniridia fibrosis syndrome, thus improving the long term vision of anridia patients. This work is supported by Aniridia Foundation International. </li></ul> | <ul>
<li><strong>Yan Wang, M.D.</strong> Â Laboratory Manager (M.D., China Medical University, China). Posterior capsular opacification<br></li><li><strong>Samuel Novo, BS</strong>Â Graduate Student (BS, University of Maryland, College Park) The regulation of inflammation post cataract surgery
</li><li><strong>Adam Faranda </strong>Graduate Student (BA, Goucher College; MS, University of Delaware) Gene regulatory networks controling PCO<br></li><li><strong>Imane Assakhi</strong> Graduate Student ECM in PCO<br></li><li><strong>Hunter Angle</strong> Graduate Student Wnt signaling in ocular fibrotic diseases<br></li><li><strong>Aarthi Krishan</strong> Graduate Student (BPT Saveetha University: MS State University of NY, Buffalo) Mechanisms of PCO and Corneal keratopathy<br></li><li><strong>Mary McArtor, </strong>Undergraduate BS Biological Sciences major (University of Delaware, USA) posterior capsular opacification<br></li><li><strong>Ananya Garg</strong>, Undergraduate BS Biological Sciences major (University of Delaware, USA) posterior capsular opacification<br></li><li><strong></strong><strong>Rabiul Rafi</strong>, Undergraduate Biological Sciences major (University of Delaware, USA) lens biomechanics<br></li></ul> | <p></p><p>​Mahbubul
H. Shihan, Samuel G. Novo, Sylvain Le Marchand, Yan Wang and <strong>Melinda K. Duncan</strong> (2021)<a href="https://www.sciencedirect.com/science/article/pii/S2405580821000108"> A simple method for quantitating confocal fluorescent images</a> <em>Biochemistry and Biophysics Reports</em> 25:100916<br></p><p></p><p></p><p>Anna Voskresenskaya, Nadezhda Pozdeyeva, Yevgeniy
Batkov, Tatyana Vasilyeva, Andrey Marakhonov, Richard A. West, Jeffrey L.
Caplan, Ales Cvekl, Yan Wang and <strong>Melinda
K. Duncan</strong> (2020)<a href="https://pubmed.ncbi.nlm.nih.gov/33248069/"><em> Morphometric analysis of the lens in human aniridia and mouse Small eye</em></a><em> Experimental Eye Research</em>
in press.</p><p></p><p></p><p>Mahbubul H. Shihan,
Mallika Kanwar, Yan Wang, Erin E. Jackson, Adam P. Faranda, and <strong>Melinda K. Duncan</strong> (2020)<a href="https://www.sciencedirect.com/science/article/pii/S0945053X20300147?via%3Dihub"> Fibronectin has multifunctional roles in posterior capsular opacification (PCO)</a> <em>Matrix biology</em> 90:79-108</p><p></p><p></p><p>Mahbubul H. Shihan, Samuel G. Novo, and <strong>Melinda
K. Duncan</strong> (2019) <a href="https://www.ncbi.nlm.nih.gov/pubmed/31328581">Cataract surgeon viewpoints on the need for novel preventative anti-inflammatory and anti-posterior capsular opacification therapies </a><em>Current
Medical Research and Opinion </em>35(11):1971-1981</p><p></p><p></p><p>Jiejing Li, Mark Perfetto, Christopher Materna, Rebecca
Li, Hong Thi Tran, Kris Vleminckx, <strong>Melinda
K. Duncan</strong> and Shuo Wei (2019), <a href="https://www.ncbi.nlm.nih.gov/pubmed/31371771">A new transgenic reporter linereveals Wnt-dependent Snail2 re-expression and cranial neural crestdifferentiation in Xenopus </a>bioRxiv520726; <em>Scientific Reports</em>; <strong>9</strong>(1) 11191</p><p></p><p>
</p><p>Jian Jiang, Mahbubul Shihan, Yan Wang and <strong>Melinda K. Duncan</strong> (2018) <a href="https://iovs.arvojournals.org/article.aspx?articleid=2707436">Lens epithelial cells initiate the inflammatory response following cataract surgery</a>.  <em>Investigative Ophthalmology and Visual Sciences </em><strong>59</strong>, 4986-4997</p>
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</p><p>Yichen Wang, Priyha Mahesh, Yan Wang, Samuel G. Novo, Mahbubul H. Shihan, Brielle, Hayward-Piatkovskyi, and <strong>Melinda K. Duncan</strong> (2018) <a href="https://doi.org/10.1016/j.exer.2018.06.020">Spatiotemporal dynamics of canonical Wnt signaling during embryonic eye development and posterior capsular opacification (PCO).</a>Â Â <em>Experimental Eye Research<b>Â </b></em><b>17</b>, 148-158.</p>
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</p><p>Yichen Wang, Anne M. Terrell, Brittany A. Riggio, Deepti Anand, Salil A. Lachke, and <strong>Melinda K. Duncan</strong> (2017) <a href="https://www.ncbi.nlm.nih.gov/pubmed/28763805">Beta1-integrin deletion from lens activates cellular stress responses leading to fibrosis and apoptosis</a>. <em>Investigative Ophthalmology and Visual Sciences </em><strong>58</strong>, 3896-3922.</p>
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</p><p>Dylan S. Audette, David A. Scheiblin and <strong>Melinda K. Duncan</strong> (2017) <a href="http://www.ncbi.nlm.nih.gov/pubmed/27015931">The molecular mechanisms underlying lens fiber elongation. </a><em>Experimental Eye Research </em><strong>156, </strong>41-49.</p>
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</p><p><strong>Melinda K. Duncan, </strong>Yichen Wang and Christopher D. Riemann (2016) <a href="https://drive.google.com/file/d/1lZZjtyisYOy0vIjFD65rT0lKzYGv9Gip/view?usp=sharing">Aniridia fibrosis syndrome: An infrequent but potentially very serious problem in congenital aniridia</a>. <em>Eye on Aniridia Newsletter, Fall 2016 edition, </em>Aniridia Foundation International.</p>
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</p><p>Mallika Pathania, Yan Wang, Vladimir N. Simirskii, and <strong>Melinda K. Duncan</strong> (2016)<a href="http://www.ncbi.nlm.nih.gov/pubmed/27596755"> Beta1-integrin controls cell fate specification in early lens development</a>Â <em>Differentiation</em>,<strong>92,</strong> 133-147.</p>
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</p><p>Ama Sadaka, Robert A. Sisk, Okan Toygar, James M. Osher, <strong>Melinda K. Duncan</strong> and Christopher D. Riemann (2016)<a href="https://www.dovepress.com/articles.php?article_id=28971"> Intravitreal methotrexate infusion for proliferative vitreoretinopathy</a> <em>Clinical Ophthalmology </em><strong>10,</strong> 1811-1817.</p>
<p></p><p>Dylan S. Audette, Deepti Anand, Tammy So, Troy B. Rubenstein, Salil A. Lachke, Frank J. Lovicu and <strong>Melinda K. Duncan</strong> (2016) <a href="http://www.ncbi.nlm.nih.gov/pubmed/26657765">Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression</a>  <em>Development </em><strong>143,</strong>:318-328.
</p><p>Lei Lyu, Shuhong Jiang, Min-Lee Chang, Yumei Gu, <strong>Melinda K. Duncan</strong>, Ales Cvekl, Wei-Lin Wang, Saima Limi, Lixing W. Reneker, Linfang Du, Fu Shang, Elizabeth A. Whitcomb, Allen Taylor (2016)<a href="http://www.ncbi.nlm.nih.gov/pubmed/26590164"> p27 stabilization due to an unfolded protein response interferes with lens fiber denucleation and causes cataract</a> <em>Faseb J. </em><strong>30,</strong> 1087-1095.
</p><p>Abby L. Manthey, Anne M. Terrell, Salil A. Lachke, Shawn W. Polson, and <strong>Melinda K. Duncan</strong> (2014) <a href="http://www.sciencedirect.com/science/article/pii/S2213596014001044">Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis</a> <em>Genomics Data; Data in Brief</em> <strong>2, </strong>369-374.
</p><p>Abby L. Manthey, Anne Terrell, Yan Wang, Jennifer R. Taube, Alisha R. Yallowitz, and <strong>Melinda K. Duncan</strong> (2014) <a href="http://www.ncbi.nlm.nih.gov/pubmed/25082886">The Zeb proteins, deltaEF1 and Sip1, may have distinct functions in lens cells following cataract surgery</a><em><a href="http://www.ncbi.nlm.nih.gov/pubmed/25082886"> </a>Investigative Ophthalmology and Visual Sciences, <strong>55, </strong></em>5445-5455<em>.</em>.
</p><p>David A. Scheiblin, Junyuan Gao, Jeffrey L. Caplan, Vladimir N. Simirskii, Kirk J. Czymmek, Richard T. Mathias  and <strong>Melinda K. Duncan </strong>(2014)<a href="http://www.ncbi.nlm.nih.gov/pubmed/24607497"> Beta-1 integrin is important for the structural maintenance and homeostasis of differentiating fiber cells</a> <em>International Journal of Biochemistry and Cell Biology, </em><strong>50, </strong>132-145
</p><p>Mallika Pathania, Elena V. Semina, and <strong>Melinda K. Duncan </strong>(2014)<a href="http://www.ncbi.nlm.nih.gov/pubmed/24526906"> Lens extrusion from <em>Laminin alpha 1 </em>mutant zebrafish</a> <em>The Scientific World Journal-Developmental Biology</em>, 524929. doi: 10.1155/2014/524929. eCollection
</p><p>Fahmy A. Mamuya, Yan Wang, Victoria H. Roop, David A. Scheiblin, Jocelyn C. Zajac and <strong>Melinda K. Duncan</strong> (2014) <a href="http://www.ncbi.nlm.nih.gov/pubmed/24495224">The Roles of αV Integrin in Lens EMT and Posterior Capsular Opacification</a> <em>Journal of Cellular and Molecular Medicine, </em><strong>18, </strong>656-670.
</p><p>Abby L. Manthey, Salil A. Lachke, Paul G. FitzGerald, Robert W. Mason, David A. Scheiblin, John H. McDonald, and <strong>Melinda K. Duncan</strong> (2014) <a href="http://www.ncbi.nlm.nih.gov/pubmed/24161570">Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development</a> <em>Mechanisms of Development, </em><strong>131, </strong>86-110.
</p><p>Robb U. de Iongh and <strong>Melinda K. Duncan</strong> (2014) Growth factor signaling in lens fiber differentiation <em>in Lens Epithelium and Posterior Capsular Opacification</em>, Shizuya Saika, Liliana Werner and Frank J. Lovicu, editors. Springer Japan KK (Tokyo)
</p><p>Sharmila Chatterjee, Yan Wang, <strong>Melinda K. Duncan</strong> and Ulhas P. Naik (2013) <a href="http://www.ncbi.nlm.nih.gov/pubmed/23667656">Junctional adhesion molecule-A regulates vascular endothelial growth factor receptor-2 signaling-dependent mouse corneal wound healing</a>. <em>PLOS one</em> 8(5):e63674. doi: 10.1371/journal.pone.0063674
</p><p>Bhagwat V. Alapure*, Jaime K. Stull*, Zeynep Firtina and <strong>Melinda K. Duncan</strong> (2012) <a href="http://www.ncbi.nlm.nih.gov/pubmed/22713599">The Unfolded Protein Response is activated in Connexin50 mutant mouse lenses</a> <em>Experimental Eye Research </em><strong>102,</strong> 28-37
</p><p>Fahmy A. Mamuya and<strong> Melinda K. Duncan</strong> (2012) <a href="http://www.ncbi.nlm.nih.gov/pubmed/21883891">αV-β integrins and TGF-β induced EMT; a circle of regulation</a>. <em>Journal of Cellular and Molecular Medicine </em><strong>16,</strong> 445-455
</p><p>Abby L. Grabitz-Manthey and <strong>Melinda K. Duncan</strong> (2012) <a href="http://www.ncbi.nlm.nih.gov/pubmed/20868684">Focus on molecules: Smad Interacting Protein 1 (Sip1, ZEB2, ZFHX1B).</a> Experimental Eye Research. <strong>101,</strong>105-106.
</p><p><strong>Melinda K. Duncan</strong> (2011) <a href="http://www.ncbi.nlm.nih.gov/pubmed/21436425">Development. A new focus on RNA in the lens.</a> <em>Â Science </em><strong>331, </strong>1523-1524.
</p><p>Zeynep Firtina and <strong>Melinda K. Duncan</strong>. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21044701">Unfolded Protein Response (UPR) is activated during normal lens development Mechanisms of Development.</a> Gene Expression Patterns. 2011;11, 135-143.
</p><p>Geetha Parthasarathy, Bo Ma, Cheng Zhang, Celine Gongora, Samuel Zigler Jr, <strong>Melinda K Duncan, </strong>and Debasish Sinha <a href="http://www.ncbi.nlm.nih.gov/pubmed/21203897">Expression of βA3/A1-crystallin in the developing and adult rat eye.</a> Journal of Molecular Histology. 2011;<strong> </strong>42,<strong> </strong>59-69.
</p><p>Brian P. Danysh, Tapan P. Patel, Kirk J. Czymmek, David A. Edwards, Liyun Wang, Jayanti Pande, and<strong> Melinda K. Duncan</strong>. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20026402">Characterizing molecular diffusion in the lens capsule.</a> Matrix Biology. 2010;29:228–236.
</p><p>Vivek D. Desai, Yan Wang, Vladimir N. Simirskii and <strong>Melinda K. Duncan</strong>. <a href="http://dx.doi.org/doi:10.1016/j.diff.2009.09.004">CD44 expression is developmentally regulated in the mouse lens and increases in the lens epithelium after injury.</a> Differentiation. 2010;79(2):111–119.<br></p> | | | <img alt="Melinda Duncan" src="/content-sub-site/PublishingImages/people/duncanm/Duncan-Melinda-2022.jpg" style="BORDER:0px solid;" /> | |
